Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University

抄録

Five kinds of <I>N</I>-substituted 3-hydroxy-2-methyl-4(1<I>H</I>)-pyridinones, and three kinds of 1-hydroxy-2(1<I>H</I>)-pyrimidinones were synthesized. Treatment of 3-hydroxy-4(1<I>H</I>)-pyridinones with VO(acac)<SUB>2</SUB> in CH<SUB>3</SUB>OH exclusively gave CH<SUB>3</SUB>O-coordinated oxovanadium (V) complexes. On the other hand, treatment with VOSO<SUB>4</SUB> in H<SUB>2</SUB>O at pH 10 for 3-hydroxy-4(1<I>H</I>)-pyridinones and at pH 7 for 1-hydroxy-2(1<I>H</I>)-pyrimidinones afforded the corresponding oxovanadium (IV) complexes. These complexes were fully characterized by means of IR, UV-vis, <SUP>1</SUP>H-and <SUP>51</SUP>V-NMR, FAB-MS, ESR spectroscopies, and combustion analysis. From the result of the inhibitory effect of oxovanadium (IV) complexes on free fatty acid (FFA) release from rat adipocytes treated with epinephrine in the presence of glucose <I>in vitro</I>, it was revealed that bis(1,2-dihydro-4,6-dimethyl-2-oxo-1-pyrimidinolato)oxovanadium (IV) showed the highest insulin-mimetic activity. Furher, the <I>in vivo</I> insulin-mimetic activity was evaluated with streptozotocin (STZ)-induced diabetic rats. Blood glucose levels were substantially lowered from hyperglycemic to nomal levels after the treatment with bis (1,2-dihydro-4,6-dimethyl-2-oxo-1-pyrimidinolato) oxovanadium (IV) by daily intraperitoneal injections.